Background/Objective
Fixed drug eruption (FDE) is a dermatosis characterized by recurrent patches or plaques at exactly the same sites with each administration of the causative drug. Vesicles or bullae may sometimes be found, and generalized bullous fixed drug eruption (GBFDE) may be confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). This study aimed to investigate the clinical and pathologic features of FDE in Taiwan.

Methods
A retrospective analysis evaluated patients with FDE in a referral center in Taiwan covering a period of 11 years. Clinical data, suspected etiologies, and pathology/patch test results were collected. We also compared the GBFDE cases with SJS/TEN overlap or TEN cases to find differentiating clues.

Results
There were 39 FDE patients, including nine GBFDE cases. The most frequent causative drugs were non-steroidal anti-inflammatory drugs (five cases, 12.8%) and antibiotics (four cases, 10.3%). Extremities other than the hands (71.8%) were the most frequently affected sites, followed by the trunk (51.3%), mucosa (38.5%), and hands (33.3%). The average age of FDE patients was 52.2 years (median, 56 years; range, 4–86 years). Patients with GBFDE were significantly older than non-GBFDE patients (69.1±19.7 vs. 47.2±23.6, p=0.0124) and the trunk was more likely to be involved in GBFDE cases (88.9% vs. 40.0%, p=0.0197). GBFDE cases also showed tendency to have more mucosal involvement (66.7% vs. 30.0%, p=0.0631). Although similar to SJS/TEN, GBFDE cases had fewer constitutional symptoms, less mucosal involvement but had previous episodes. Histopathologically, the presence of more than two aggregated dyskeratotic keratinocytes (fire flag sign) in the epidermis was more frequently observed in SJS/TEN, whereas GBFDE had superficial and deep dermal infiltration of eosinophils and melanophages.

Conclusion
FDE is one of the specialized cutaneous drug reactions and GBFDE should be kept in mind and differentiated from SJS/TEN.